The present invention concerns a gastrointestinal probe intended for the measure of the aggressive force and deleterious effects that gastrointestinal secretions or biliopancreatic secretions and other gastrointestinal contents or forces may exert on the mucosa and surrounding tissues of oesophagus, stomach and intestines.
The gastrointestinal tract comprises a mucosal surface which is submitted to aggressive secretions and/or body forces involved in the digestion. In the stomach, the digestion is obtained by the secretion of the acid gastric juice. Presently available methods to evaluate in man the aggressive and damaging powers of digestive secretions are based on intraluminal pH measurements or on biochemical assays. Intraluminal pH measurements yield an instantaneous measure of the acidity of the gastrointestinal contents at a given location in the gastrointestinal tract. Biochemical assays measure in vitro parameters such as enzyme activities in an amount of digestive juices collected over a given period of time. These approaches only allow to measure instantaneous changes in parameters which are known or assumed to have a role in the production of tissue damages.
Examples of intraluminal pH-sensing electrodes are glass or plastic electrodes, ISFET (Ion Sensitive Field Effect Transistor) optical electrodes, combination electrodes or unipolar monocrystalline antimony electrodes (connected to a pH-meter via a cable).
The reference xe2x80x9cChemical Sensors based on Fiber Opticsxe2x80x9d, Analytical Chemistry 56(1), 16A-34A, W. R. Seitz, Easton U.S. (1984) describes devices involving a reagent phase on the end of an optic fiber. In operation, interaction with analytes leads to a change in optical properties of the reagent phase, which is probed and conducted through the optic fiber.
In particular, a class of irreversible sensors is described. The xe2x80x9cirreversiblexe2x80x9d sensing principle, in the sense of a reagent consuming system, is based on analytical reactions that consume reagent. Said xe2x80x9cirreversiblexe2x80x9d sensors can have a lifetime of months, or years but act within said lifetime as reversible systems with respect to sensor response. Said reversibility means that whenever said xe2x80x9cirreversiblexe2x80x9d sensor is transferred from a first medium, e.g. with oxygen partial pressure (a), to a second medium with oxygen partial pressure(b), and thereafter back to said first medium, said sensor back in the first medium will again record an oxygen partial pressure.
The document xe2x80x9cResearch on Gastric Multiparameter Sensors Technologyxe2x80x9d, Proceedings of ICEE Engineering in Medicine and Biology Society, vol. 14, 16-120, X. Lin et al. (1992) introduces gastric multiparameter sensor technology and describes devices based on reversible measurement principle.
Above-mentioned electrodes based upon an instantaneous and reversible measure of the intraluminal pH do not give a correct measure of the aggressive action due to the secretions and the body forces in the gastrointestinal tract.
Furthermore, the effects of other physical and biochemical factors such as enzymatic catalysis by pepsin, trypsin and other enzymes, bile secretions, osmotic forces, pressure or flow of intestinal contents, are not measured by these electrodes.
Methods to measure the irreversible and cumulative changes produced by prolonged contact with digestive secretions are not available. Such measurements should give a more direct and more accurate estimate of the expected tissue damage in several disease entities. This information is much needed because it should shed new light on pathological aspects of various diseases such as acid-peptic diseases (reflux oesophagitis, peptic ulcer, gastritis, duodenitis, Zollinger Ellison syndrome) and diseases where other enzymatic activities, such as tryptic activity, may play a role (coeliac disease, inflammatory bowel disease). As presently available methods do not allow to obtain this much needed information, the present invention is developing a gastrointestinal probe which allows to measure the irreversible and cumulative changes produced upon a substrate in the digestive tract (acidity enzyme activity and other physico-chemical forces).
The main aim of the present invention is to obtain a gastrointestinal probe which may measure by an irreversible change of the sensitive material the effect of the cumulative aggressive force that digestive secretions and other body forces may exert upon the mucosa and surrounding tissues of the digestive tract.
The present invention concerns a gastrointestinal probe comprising a sensitive material which is able to be connected to electrical or optical readout means or measurement means, wherein said sensitive material undergoes an irreversible change when it is submitted to the cumulative action of the external medium, in such a manner that the irreversible change can be measured and/or recorded by said electrical or optical readout or measurement means.
The term xe2x80x9cirreversible change of the sensitive materialxe2x80x9d means a physical or chemical irreversible modification of said material.
The xe2x80x9ccumulative action of the external mediumxe2x80x9d means the cumulative aggressive forces (physical and biochemical force due to enzymatic catalysis, pH modification, bilious secretion, osmotic force, pressure or flow of intestinal content) that gastrointestinal secretions and biliopancreatic secretions and other gastrointestinal contents or forces may exert on the mucosa and surrounding tissues of the gastrointestinal tract (oesophagus, stomach and intestine).
According to the invention, said irreversible change of the said sensitive material is a chemical or physical modification of said sensitive material selected from the group consisting of swelling, hydrolysis, molecular modifications (preferably due to absorption of one or more elements from the external medium), loss, release, decomposition, modification of refractive index, light absorption or any other property of said sensitive material which may be measured or recorded by electrical or optical devices.
Advantageously, the said sensitive material is part of a matrix composed of one or more electrically conducting composite material(s).
Preferably, said matrix comprises:
a polymeric sensitive material showing characteristics of an irreversible change when placed in the area of the digestive tract under examination and exposed to the prolonged action of aggressive secretions and/or body forces involved in the digestion.
an electrically conducting material, preferably evenly dispersed in the polymeric material, in order to create a conductive path which allows the electrical monitoring of the irreversible change of the matrix,
possibly, a surrounding protective layer having a retarding effect on the irreversible change of the matrix.
Said polymeric sensitive material is selected from the group consisting of pyridine, styrene, methacrylate based polymers and copolymers, acid resistant polymers, polymeric compositions used as drug coating for pH dependant delivery of active compounds and/or a mixture thereof.
Said electrically conductive material is preferably chosen among the group consisting of metals, semi-conducting oxides, carbon, electronically conducting polymers and/or a mixture thereof.
The present invention concerns also the catheter which comprises the gastrointestinal probe according to the invention, and possibly the electrical or optical readout measurements or devices for measurement.
The form and the size of the gastrointestinal probe and its catheter can differ according to the specific application or introduction pathways into the gastrointestinal tract.
It is another object of the present invention to disclose a production process of the gastrointestinal probe according to the invention wherein the connections between the sensitive material and the electrical or optical readout measurement or devices for measurement are obtained by microelectronic patterning techniques.
According to a preferred embodiment of the invention, said micro-electronic patterning techniques comprise the following steps: photolithographic patterning a substrate followed by evaporation, sputtering, plating or deposition, using conventional physical or chemical techniques, of a metallic conductor pattern and insulation layers and deposition of a sensitive material upon at least one portion of said photolithographic patterning substrate.
According to another preferred embodiment of the invention, said micro-electronic patterning techniques comprise the following steps: screen printing of metallic conductor and insulator patterns on an inert substrate, preferably chosen among the group consisting of alumina, oxidized silicon, flexible polymer substrates and/or a mixture thereof and deposition of a sensitive material upon at least one portion of said substrate.
Preferably, several compounds are added to the sensitive material in order to facilitate the deposition of said material upon its substrate.
Other deposition steps such as moulding may also require additives well known by a person skilled in the art.
Another object of the present invention concerns the use of the gastrointestinal probe according to the invention for the measure of the aggressive forces produced by secretions and/or body forces involved with the digestion in the gastrointestinal tract.
According to one preferred embodiment, such probes can be used as a NON-continuous measurement device. In this case, the probe is introduced in the patient""s gastrointestinal tract and removed the next day for instance. Then the measure is achieved by means of external electronical or optical devices to determine the degree or severity of the aggression. Thus, the electronical or optical devices are not introduced into the patient""s gastrointestinal tract.
According to another preferred embodiment, the probe of the invention can be used as a continuous measurement device.
Preferably, the gastrointestinal probe according to the invention is used in the stomach, in the oesophagus, and in the small or large intestine.